SB L3 - Neurogenisis Flashcards
What is adult neurongenisis
the ability of the adult brain to generate new neurones
proliferation, migration, differentiation, survival, intergration - into a funcitoning network
Does adult neurogenesis take place all over the brain?
no - localized to discrete brain regions
e.g. hippocampus
Define stem cells
Progenitor cells
Precursos cells
Stem cells – able to proliferate, to self-renew and to differentiate to multiple lineages
Progenitor cells – proliferate, differentiate but do not self-renew
Precursor cells – both stem cells and progenitor cells
major relay station for information from the cortex to other regions is…..
Hippocampus - key place for neurogenisis
Lateral ventricles are a site where neurogenesis occurs,. Subventricular zone gives rise to cells that migrate to the hippocampus.
What are the key cells for neurogenesis, where are they found?
Granule cells in the dendate gyrus.
Theses are replaced with the new neurons from neurogenesis.
Hip is associates with …………… and ………….
also connected ro ……………… and ………………. associated with what funcitons?
Hippocampus is related to learning and memory but also anxiety because it has reciprocal connections with
- prefrontal cortex (mood)
- amygdala (emotion and fear).
What does BrdU stand for?
What is it?
Bromodeoyuridine
-
What does BrdU stand for?
What is it?
Bromodeoyuridine
- a uridine derivative that can be incorporated specifically into DNA in place of thyamine
(it’s not something endogenous so we know where it comes from)
What do we do with the BrdU?
You can take the brain slice and use antibodies to see the cells
What does BrdU show?
What else should you look for?
numbers of cells proliferating and dividing (but no whether they are neurones/ will they be intergrated into a funcitoning network?)
Look for markers of neuronal cells (they express different markers at different stages of development)
What did ……….REF ….find about adult neurogenisis from 14C?
Spalding et al. 2013:
- used concentration of nuclear bomb-test-derived 14C in genomic DNA to look at generation of hippocampal cells in humans
- one third of hippocamal neurones is subject to exchange
-700 new neurons are added per day, (annual turnover of 1.75% of the neurons within the renewing fraction), with a modest decline during aging.
(this is much higher than rodents)
5 factors that reglate neurogenisis
we won’t focus in these but good examples
- Intrinsic cell programming
- Transcription factors involved in initiation of proliferation
- Neurotransmitters
- 5-HT, NA, DA - Neurotrophic factors
- BDNF, NGF, VEGF - Corticosteroids
- Environmental stimuli
5 factors that reglate neurogenisis
we won’t focus in these but good examples
- Intrinsic cell programming
- Transcription factors involved in initiation of proliferation
- Neurotransmitters
- 5-HT, NA, DA - Neurotrophic factors
- BDNF, NGF, VEGF - Corticosteroids
- Environmental stimuli
Where can we find 5HT neurones in the DG?
What is the effect of activation/blockage?
What is the effect of lesioning?
subgranular layer
Activation/blockade of multiple 5-HT receptors alters proliferation
Lesioning 5-HT neurons reduces the proliferation of hippocampal cells
effect of NA on nerogenesis?
NA depletion significantly decreases proliferation (but not survival) in SGL
effect of DA on neurogenesis?
DA reported to have both +/- role in regulating proliferation in SVZ
effect of ACh on neurogenisis?
Lesioning forebrain ACh neurons reduces, and blockade of ChE increases, proliferation
What can we see by comparing the locolization of neurotransmitters?
Perhaps neurotransmitters define the localization where neurogenesis occurs.
What are neurotrophins?
Provide trophic or neurtriant support to neurones and act as a growth factor
thought to stimulate neurogenisis.
Neurotrophic growth factor family has …. proteins (including …………)
4 proteins
(including brain derived neurotrophic factor)
These proteins have structural similarity. All produced from a pre-protein chopped to make a mature protein.
Where do neurptrophic factors bind?
to tropomyosin receptor kinases TrkA, B and C
BDNF binds to
Trk B receptor.
When neurotrophic growth factors bind what pathways are activated (3)
- Protein kinases B factor crucial for survival
- PLC gamma for activity dpendent plasticity
- ERK differentiation and survival
What is the endogenous GC in rats?
cortisone
